The goal of the University of Iowa CORT is to develop new methods of forestalling post-traumatic osteoarthritis (PTOA) through a multi-disciplinary translational approach including basic science, bioengineering, imaging, and clinical research. The central theme is that joint injuries initiate a sequence of biologic events that lead to PTOA and that new treatments of joint injuries will minimize these deleterious events and promote joint healing. The specific aims are to: 1) advance understanding of the pathogenesis of PTOA, 2) develop and refine reliable quantitative measures of severity of joint injuries, including measures of structural damage and biologic response to joint injury, and 3) apply the advances in understanding of the pathogenesis of PTOA and assessment of joint injury to new methods of forestalling PTOA. The four CORT projects are: 1. Cartilage Extracellular Matrix Fragments and Trauma-Induced Chondrolysis, an in vitro study that will identify pathways responsible for propagation of cell damage following injury;2. Acute versus Chronic Mechanical Damage in the Etiology of PTOA, an experimental study that will define the role of loading of injured joints in causing OA, and new methods for preventing OA in injured joints;3. Validation and Application of MRI Biomarkers in Assessing Articular Cartilage Health, a clinical and experimental study of non-fracture cartilage injury that will help define the ability of non-invasive measures to assess the severity of cartilage damage, that will identify which synovial fluid markers of acute joint injury reflect that damage, and that will test the hypothesis that decreased loading accelerates restoration of injured joint surfaces;and 4. Quantifying Injury Severity to Assess the Risk for Post-Traumatic OA, a clinical study of intra-articular fractures that will examine the hypothesis that new quantitative measures of the severity of structural joint injury predict clinical outcomes. This project also will conduct a multi-center study of the severity of joint injury, in preparation for clinical trials of molecular interventions to minimize the risk of OA following joint injury. The four projects will be supported by an administrative-biostatistics core, a biomechanics-imaging core, and a tissue and experimental modeling core. Relevance to Public Health: Osteoarthritis (OA) is the most common joint disease and is among the most important causes of pain, disability, and economic loss. About 12% of OA arises following joint trauma. The risk of OA ranges from 20% to 50% or more following many common joint injuries;and, despite evolving surgical methods of treating joint injuries, this risk has not decreased appreciably in the last 20 years. The basic science, bioengineering and clinical research in this CORT will lead to new biologic and improved minimally invasive operative treatments of joint injury that will forestall OA and thereby improve the lives of hundreds of thousands of people.